Enantioselective synthesis of enantiomerically enriched compounds

ABSTRACT

Method of preparing an enantiomerically enriched compound of formula (II) comprising enantioselective hydrogenation of a compound of general formula (I): where W, X and Z have the meanings indicated in the description, to give a compound of general formula (II): where W, Y, T and C* have the meanings indicated in the description, in the presence of a catalyst or its suitable precursor based on Rh, Ru or Ir, having an oxidation state of 0, +1 or +2, and containing at least one enantiomerically enriched chiral ligand.

The present invention relates to a new method of synthesis ofenantiomerically enriched compounds.

(R)-tolterodine of Formula (T)

in the form of salt of tartaric acid, has recently been launchedsuccessfully on the world market as a drug against urinary incontinence.

Moreover, document U.S. Pat. No. 6,310,103 describes the correspondingenantiomer (S)-tolterodine of formula (T′) and its salts as drugs foruse in the treatment of disorders of the urinary and gastrointestinaltracts.

The methods of synthesis for the production of (R,S)-tolterodine, itsenantiomers and the corresponding salts described in patent EP-A-0 325571 include numerous steps (at least 6). Some of these steps involve theuse of toxic or dangerous reagents and solvents and often give lowyields. Moreover, production of the pure enantiomer, which is thepharmacologically active principle, employs separation by formation ofdiastereomeric salts which, by its nature, can only give a yield below50%.

A person skilled in the art will be aware that to reduce the productioncosts it would be useful to recover the (S) enantiomer by repeatedracemizations and separations, but to the best of our knowledge a methodof this type has never been described. Alternatively, it would be usefulto find a method of synthesis that can lead to a finished product thatis already enantiomerically pure or at least substantially enriched inthe desired enantiomer. Apparently, this has been the object ofintensive research.

Patent application WO 0149649, equivalent to the already cited U.S. Pat.No. 6,310,248, describes a synthetic route that leads to anenantiomerically enriched 4-phenyl-6-methyl-chroman-2-one [(II); Y+T=O],with an enantiomeric excess (e.e.) of 89%. According to that document,the chromanone in the example had an absolute (S) configuration andcould be converted to tolterodine enantiomerically enriched in the (R)enantiomer by known methods. In fact, according to the presentinventors, the said chromanone should lead to tolterodineenantiomerically enriched in the (S) enantiomer. It can, however, beconjectured that changing the absolute configuration of the chiralreagent used (for example (S)-MeCBS instead of (R)-MeCBS) might lead tothe (R) enantiomer. Nevertheless, this method also involves numeroussteps and the use, as chiral reagent, of a boron derivative (MeCBS) thatis expensive and not very suitable for production on an industrialscale.

Not even the synthesis described in J. Org. Chem. 63, 8067 (1998) iswithout drawbacks, because it uses reagents that are difficult to handleon a large scale and also involves the use of a chiral auxiliary thatmust then be recovered and recycled. Moreover, that article alsodescribes the difficulties inherent in the synthesis of tolterodine orits suitable precursors by asymmetric hydrogenation (page 8067, leftcolumn, second paragraph), thus dissuading a person skilled in the artfrom this synthetic route.

Some of the present inventors have also investigated a method ofhydroformylation reported in Org. Process Res. & Developm. 6, 379(2002); however, this reaction, which proved industrially advantageousfor producing the racemic product (R,S)-tolterodine, gave ratherunsatisfactory results in enantioselective synthesis, which were alsoconfirmed by the results recently reported in patent application WO0204399. In fact tolterodine or its precursors are obtained with e.e.<10%, with negligible enrichment in the desired enantiomer.

Finally, a recent article [Tetrahedron Letters, 40, 3293 (1999)]described an asymmetric hydrogenation, in the presence of chiraldiphosphinic catalysts of Rh or Ru, of alkaline or alkylammonium saltsof suitable 3,3-diaryl acrylic acids to obtain 4-arylcoumarines. In thatarticle it is emphasized that good enantiomeric excess (e.e.) is onlyobtained on particular, appropriately substituted substrates and inparticular reaction conditions.

In its turn, the asymmetric hydrogenation of substituted 3,3-diarylallylic alcohols described in Tetrahedron Asymmetry, 6, 835 (1995) hasthe drawback that it involves reaction times of several days and the useof quite high hydrogen pressures. Therefore it cannot be usedindustrially.

Surprisingly, the present inventors have now found an asymmetricsynthetic route that does not have the aforesaid shortcomings and isbased on a reaction of hydrogenation in the presence of a catalyst basedon Rh, Ru or Ir, having an oxidation state of 0, +1 or +2, andcontaining at least one chiral ligand.

In one of its aspects the present invention therefore relates to amethod of preparing an enantiomerically enriched compound of formula(II), characterized in that it comprises the enantioselectivehydrogenation of a compound of general formula (I):

where

W is a CH₂ group or a C═O group;

X is a hydroxy, C₁-C₆ alkoxy, benzyloxy, C₁-C₆ acyloxy,O-tetrahydropyranyl, O-tetrahydrofuryl group, a group O⁻M⁺ in which M⁺is a cation of an alkali metal or a cation N⁺R₁R₂R₃ where R₁, R₂ and R₃,which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈ cycloalkylor benzyl group;

Z, when W is CH₂, is a hydroxy group whereas, when W is C═O, it is ahydroxy, C₁-C₆ alkoxy, benzyloxy or N(iC₃H₇)₂ group, a group O⁻M⁺ inwhich M⁺ is a cation of an alkali metal or a cation N⁺R₁R₂R₃ where R₁,R₂ and R₃, which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈cycloalkyl or benzyl group;to give a compound of general formula (II):

where

W has the meanings indicated above;

Y has the same meanings indicated above for X;

T has the same meanings indicated above for Z; or

when W is C═O

Y and T, together, are an oxygen atom; and

C* indicates the enantiomerically enriched chiral carbon atom;

in the presence of a catalyst or its suitable precursor based on Rh, Ruor Ir, having an oxidation state of 0, +1 or +2, and containing at leastone enantiomerically enriched chiral ligand.

In a particularly preferred embodiment, the method of the presentinvention also includes the conversion of the compound of formula (II)thus obtained, in which Y, W and T are not already OH, CH₂ and N(iC₃H₇)respectively, to tolterodine enantiomerically enriched in the desiredenantiomer.

In the present description the term “precursor” of a catalyst indicatesa compound that is transformed to the desired catalyst in the presenceof hydrogen.

The enantioselective hydrogenation according to the present inventioncan be carried out advantageously in homogeneous phase or in multiphaseconditions, for example solid-liquid, immiscible liquid-liquid.

The catalyst and/or its precursor can be used as they are or immobilizedon a suitable inorganic or organic support, for example silica,heteropolyacids/silica, heteropolyacids/alumina, zeolites, resinscontaining sulphonic, phosphonic and similar groups.

Typically, the molar ratio between the catalyst, or its precursor, andthe compound of formula (I) is between 1/10 and 1/30 000. Preferably thesaid ratio is between 1/10 and 1/10 000. Even more preferably it isbetween 1/100 and 1/5000.

Typical examples of enantiomerically enriched chiral ligands accordingto the present invention are the mono- and diphosphinic, mono- anddiphosphitic, mono- and diaminophosphinic ligands, such as the ligandscontaining a monophosphinic group and a C₁-C₆ alkoxy, benzyloxy,oxazoline, pyrrolidine or piperidine group, a group NR₁R₂, where R₁ andR₂, which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈cycloalkyl or benzyl group, a group NHCOR₃ or NHSO₂R₃ where R₃ is aC₁-C₈ alkyl, phenyl or tolyl group.

If necessary, the valence state of the metal of the catalyst accordingto the present invention is supplemented by at least one ancillaryco-ligand.

Examples of suitable catalysts according to the present invention are:

Ru(TMBTP)(OCOCF₃)₂; Ru(TMBTP)(p.cymene)I₂; Ru(TMBTP)(p.cymene)Cl₂;Ru(BINAP)(OCOCF₃)₂; Rh(COD)(Chiraphos)ClO₄; Rh(NBD) (Chiraphos)ClO₄;where TMBTP denotes2,2′,5,5′tetramethyl,3,3′bis(di-phenylphosphine),4.4′bithiophene, BINAPdenotes 2,2′bis(diphenyl-phosphine)1,1′binaphthyl, Chiraphos denotes 2,3bis(diphenyl-phosphine)butane, COD denotes cyclooctadiene, and NBDdenotes norbornadiene.

Advantageously, the enantioselective hydrogenation according to thepresent invention is carried out at a pressure of 1-100 bar andpreferably of 1-20 bar. Typically, during hydrogenation, the temperatureis 20-100° C. and, preferably, 20-60° C. In a preferred embodiment,hydrogenation is carried out in the presence of a suitable solvent or asuitable solvent mixture. Typical examples of suitable solvents areC₁-C₄ alcohols, tetrahydrofuran, methylene chloride, C₁-C₄ alkylaromatics or C₆-C₁₀ alkanes and their mixtures with water.

In the compounds of formula (I), W is preferably a C═O group; X is,preferably, OH or O⁻M⁺ in which M⁺ has the meanings already indicatedabove; Z is, preferably, OH, N(iC₃H₇)₂ or O⁻M⁺ in which M⁺ has themeanings already indicated above.

In the compounds of formula (II), W is preferably a CH₂ or C═O group; Yis, preferably, OH or O⁻M⁺ in which M⁺ has the meanings alreadyindicated above; T is OH, N(iC₃H₇)₂ or O⁻M⁺ in which M⁺ has the meaningsalready indicated above. An especially preferred meaning is that inwhich Y and T, together, represent an oxygen atom of the lactone offormula (IIA)

The compounds of formula (I) can be prepared by methods similar to thosealready known for preparing similar products. For example, when X═OH orO⁻M⁺, W is a C═O group and Z is a hydroxy, O⁻M⁺, alkoxy or N(iC₃H₇)₂group; a convenient synthesis with high yield is that shown in Scheme 1.If necessary, this is then followed by treatment with a suitable base,for example an alkaline, ammoniacal hydroxide or a tetraalkylammoniumhydroxide, to salify the acid group and the phenolic group.

When the compound of formula (II) obtained by enantioselectivehydrogenation is tolterodine (Y═OH, W═CH₂ and T=N(iC₃H₇)₂) enriched inthe desired enantiomer, this is isolated by known techniques, forexample by fractional crystallization of one of its salts, for examplethe tartrate, until the required pharmaceutical specifications are met.

However, when this is not tolterodine, the compound of formula (II)enriched in the desired enantiomer is easily converted to tolterodine byknown techniques, for example those described in patents U.S. Pat. No.5,922,914, WO 01/49 649 and EP-A-0 325 571 or by the techniquesdescribed in the following examples.

The following examples serve the purpose of illustrating the invention,though without limiting it in any way.

EXAMPLE 1 6-methyl-4-phenyl-chromen-2-one (I; X+Z=O; W═CO)

2-Bromo-4-methylphenol (2.4 ml; 19.7 mmol), Et₄NCl (2.2 g; 13.3 mmol),Cy₂(Me)N (4.2 ml; 19.7 mmol) and Pd(OAc)₂ (59 mg; 0.26 mmol) were addedunder nitrogen at room temperature to a solution of methyl cinnamate(2.1 g; 13.1 mmol) in dimethylacetamide (40 ml). The reaction mixturewas stirred at 95° C. for 48 h, then cooled and filtered on celite. Thesolution was diluted with Et₂O and washed 3 times with H₂O. The organicphase was dried over Na₂SO₄ and the solvent was evaporated under vacuum.GC-MS showed a conversion of 94%.

The raw reaction product was purified by flash chromatography. (SiO₂,n-hexane:Et₂O 7:3) and the fractions collected were crystallized fromEt₂O/n-hexane to give pale yellow crystals (2.4 g; 77% yield).m.p.=132-134° C.

¹H NMR (400 MHz, CDCl₃) δ 2.34 (s, 3H, OCH₃), 6.36 (s, 1H, CH),7.25-7.38 (m, 3H), 7.44-7.47 (m, 2H), 7.52-7.56 (m, 3H);

¹³C NMR (400 MHz, CDCl₃) δ 21.17; 115.43; 117.30; 118.917; 126.93;128.662; 129.09; 129.82; 133.15; 134.11; 135.62; 152.55; 155.86; 161.24.

EXAMPLE 2 6-methyl-4-phenyl-chroman-2-one (IIA)

A glass cylinder placed in a steel autoclave was loaded with6-methyl-4-phenyl-chromen-2-one (1 g; 4.2 mmol), [Rh(COD)Cl]₂ (104.5 mg;0.2 mmol), (S,S)-Chiraphos (180.8 mg; 0.4 mmol), CH₃OH (10 ml) and NaOH4N (2.1 ml), then it was evacuated and the autoclave was pressurized to12 bar with H₂. The reaction mixture was stirred at 50° C. for 24 h,then cooled to room temperature and the gas was removed. The solvent wasremoved in a rotary evaporator and the raw product, absorbed in H₂O, waswashed with CH₂Cl₂ (2×30 ml), the aqueous phase was then acidified with6N HCl to pH=1-2 and was then extracted with CH₂Cl₂ (30 ml×3). Theorganic phases were combined and dried over Na₂SO₄, filtered on celiteand the solvent was evaporated at reduced pressure.

GC of the raw product (DetTBuSilβCDX column 25 m, carrier gas N₂, Tinitial=100° C., initial isotherm time=1, heating rate=2, T final=200°C., final isotherm time=10, flow 2, N₂ pressure=30 psi) showed thatconversion was 96% and e.e. =80% enriched in the enantiomer at lowerretention time to which the absolute (S) configuration was attributed[(S) enantiomer retention time=46.12 min, (R) enantiomer retentiontime=48.55 min, retention time of 6-methyl-4-phenyl-chromen-2-one=53.05min]. ¹H NMR in CDCl₃ of the raw product showed that the product was amixture of (IIA) and the corresponding uncyclized product (II; Y=T=OHand W═CO) in a ratio of 1:6, approximately, and that in time the openform cyclizes spontaneously and that this cyclization is complete whenoperating under reflux for 4 h in toluene in the presence of catalyticamounts of pTsOH acid.

The raw 6-methyl-4-phenyl-chroman-2-one (IIA) was purified by flashchromatography (SiO₂, hexane:Et₂O 7:3) to give 850 mg of a white solid(yield: 84%). Dissolving the product in hot CH₃OH and then cooling, 170mg (yield: 20%) of white needles of product (S) (IIA) were obtained,with e.e. >99% [retention time=46.12 min], as determined by GC analysis;[α]_(D) ²⁰=−2.8 (CHCl₃, c=1.44), m.p.=103-105° C.

¹H NMR (CDCl₃, 400 MHz), δ 2.26 (s, 3H); 2.99 (dd, J=6.4, 16.4 Hz, 1H);3.06 (dd, J=6.4, 16.4 Hz, 1H); 4.30 (t, J=6.4 Hz, 1H); 6.78 (bs, 1H);7.00-7.18 (m, 4H); 7.28-7.38 (m, 3H);

¹³C NMR (CDCl₃, 100.57 MHz), δ 21.24; 37.56; 41.14; 117.07; 125.52;127.73; 127.81; 129.31; 129.50; 134.51; 140.68; 140.78; 167.98.

EXAMPLES 3-7 6-methyl-4-phenyl-chroman-2-one (IIA)

Following the same procedure as in Example 2 but with differentcatalysts and different substrate/catalyst molar ratios, the resultspresented in Table 1 were obtained. The predominant enantiomer had theabsolute (S) configuration. TABLE 1

con- ver- sion ee ML S/C T P t % (%) [Rh(COD)Cl₂(S,S)Chiraphos 200/1 50°C. 12 24 70% 50% bar h 2000/1 50° C. 12 24 36% 50% bar h[Rh(nbd)BF₄](S,S)Chiraphos 1000/1 50° C. 12 24 11% 20% bar h[RU(II)-(S)-(−)- 100/1 50° C. 12 24 22% 44% BINAP(OAc)₂ bar h[Ru(TFA)₂(+)-TMBTP] 100/1 50° C. 12 24 90% 80% bar h

EXAMPLE 8 6-methyl-4-phenyl-chroman-2-one (IIA)

Following the same procedure as in Example 2 but with the catalyst[Ru(TFA)₂(−)TMBTP] with a substrate/catalyst molar ratio of 100/1, ayield of 87% and e.e. of 81% were obtained after chromatographicpurification. The predominant enantiomer had the (R) absoluteconfiguration.

EXAMPLE 9 (S)-Tolterodine (formula T′)

Following procedure similar to that described in patent U.S. Pat. No.5,922,914, a solution of 100 mg (0.42 mmol) of (IIA), having [α]_(D)²⁰=−2.8 (CHCl₃, c=1.44) and prepared according to the preceding Example2, in anhydrous toluene (3 ml), was placed in a 100-ml two-necked flaskthat had been flamed beforehand. A solution of 1 M. DIBAL in toluene(440 μl, 0.44 mmol) was added dropwise to this solution, under N₂ and at−25° C.

The reaction was monitored by GC-MS and was stopped with 3 ml of ethylacetate at −25° C. after 5 h, when GC-MS showed there was formation of6-methyl-4-phenyl-chroman-2-ol at 89%, together with unreacted startingproduct (7%) and a product of further reduction[3-phenyl-3(2′hydroxy,5′methyl)phenyl-propan-1-ol] (4%). 3 ml of a 23%citric acid solution was added. The solution was stirred at roomtemperature over night. The organic phase was separated and washed withH₂O, dried over Na₂SO₄, filtered and the solvent was removed byevaporation at reduced pressure.

The raw product thus obtained was placed in a glass cylinder in anautoclave. CH₃OH (5 ml), Pd/C₅% (20 mg), (Pr^(i))₂NH (147 μl, 1.05 mmol)and H₂ were added at 5 atmospheres. The reaction was continued for 12 hat 48° C. The temperature was brought back to room temperature and theautoclave was depressurized by eliminating the gas. After filtration ofthe catalyst on celite, a GC-MS analysis was carried out, which showed6-methyl-4-phenyl-chroman-2-ol (2%), (IIA) 5%,[3-phenyl-3(2′hydroxy,5′methyl)phenyl-propan-1-ol] (16%), and(S)-tolterodine (77%). The raw product was purified by flashchromatography on SiO₂ (hexane:EtOAc(7:3)/Et₃N 98:2) to give acolourless oil (100 mg; 73%); [α]_(D) ²⁰=−23 (c=1.5; CH₃OH).

¹H NMR (CD₃OD, 400 MHz), δ 0.97 (d, J=2 Hz, 3H); 0.99 (d, J=2 Hz, 3H);2.1-2.2 (m, 2H); 2.17 (s, 3H); 2.39-2.45 (m, 2H); 3.02 (m, 1H); 4.32 (t,J=7.6 Hz); 6.63 (d, J=7.8 Hz, 1H); 6.78 (dd, J=2.0, 8.2 Hz, 1H); 6.90(d, J=2.3, 1H); 7.09-7.31 (m, 5H);

¹³C NMR (CD₃OD, 100.57 MHz), δ 20.32; 20.79; 37.48; 42.73; 45.95: 48.79;116.26; 126.81; 128.27; 129.11; 129.24; 129.41; 132.47; 164.38; 153.74.

EXAMPLE 10 (S)-tolterodine D-tartrate

D-tartaric acid (34.5 mg; 0.23 mmol) was added to a solution of(S)-tolterodine (75 mg; 0.23 mmol), prepared according to the precedingExample 9, in EtOH (5 ml). The mixture thus obtained was heated to about50° C., filtered while hot to remove a slight turbidity, and thenconcentrated to dryness at reduced pressure to give a white solid.m.p.=205-207° C.; [α]_(D) ²⁵=−37 (c=1, CH₃OH).

EXAMPLE 11 (R)-tolterodine L-tartrate

Following a procedure similar to that described in the preceding Example9 but starting from a sample of (R)-6-methyl-4-phenyl-chroman-2-onehaving e.e. 81%, obtained according to the preceding Example 8,(R)-tolterodine (T) was obtained at 70% yield.

The corresponding salt with L-tartaric acid, prepared and aspirated todryness, had [α]_(D) ²⁵=+29.1 (c=1, CH₃OH).

1. A method of preparing an enantiomerically enriched compound of formula (II), comprising enantioselectively hydrogenating a compound of general formula (I):

where W is a CH₂ group or a C═O group; X is a hydroxy, C₁-C₆ alkoxy, benzyloxy, C₁-C₆ acyloxy, O-tetrahydropyranyl, O-tetrahydrofuryl group, a group O⁻M⁺ in which M⁺ is a cation of an alkali metal or a cation N⁺R₁R₂R₃ where R₁, R₂ and R₃, which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈ cycloalkyl or benzyl group; Z, when W is CH₂, is a hydroxy group whereas, when W is C═O, it is a hydroxy, C₁-C₆ alkoxy, benzyloxy or N(iC₃H₇)₂ group, a group O⁻M⁺ in which M⁺ is a cation of an alkali metal or a cation N⁺R₁R₂R₃ where R₁, R₂ and R₃, which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈ cycloalkyl or benzyl group; to give a compound of general formula (II):

where W has the meanings indicated above; Y has the same meanings indicated above for X; T has the same meanings indicated above for Z; or when W is C═O Y and T, together, are an oxygen atom; and C* indicates the enantiomerically enriched chiral carbon atom; in the presence of a catalyst or its suitable precursor based on Rh, Ru or Ir, having an oxidation state of 0, +1 or +2, and containing at least one enantiomerically enriched chiral ligand.
 2. The method according to claim 1, wherein the compound of formula (II) in which Y, W and T are not OH, CH₂ and N(iC₃H₇)₂, respectively, is converted to tolterodine enantiomerically enriched in the desired enantiomer.
 3. The method according to claim 1, wherein the method is carried out in homogeneous phase or in multiphase conditions.
 4. The method according to claim 1, wherein the catalyst and its precursor are used as they are or immobilized on a suitable inorganic or organic support.
 5. The method according to claim 4, wherein the support is at least one selected from the group consisting of silica, heteropolyacids/silica, heteropolyacids/alumina, zeolites, and resins containing sulphonic and phosphonic groups.
 6. The method according to claim 1, wherein the molar ratio between the catalyst, or its precursor, and the compound of formula (I) is between 1/10 and 1/30000.
 7. The method according to claim 6, wherein the molar ratio is between 1/10 and 1/10
 000. 8. The method according to claim 6, wherein the molar ratio is between 1/100 and 1/5000.
 9. The method according to claim 1, wherein the enantiomerically enriched chiral ligand is selected from mono- and diphosphinic, mono- and diphosphitic, mono- and diaminophosphinic ligands, ligands containing a monophosphinic group and a C₁-C₆ alkoxy, benzyloxy, oxazoline, pyrrolidine or piperidine group, a group NR₁R₂, where R₁ and R₂, which may be identical or different, are a C₁-C₈ alkyl, C₃-C₈ cycloalkyl or benzyl group, a group NHCOR₃ or NHSO₂R₃ where R₃ is a C₁-C₈ alkyl, phenyl or tolyl group.
 10. The method according to claim 9, wherein optionally the valence state of the metal of the catalyst is supplemented with at least one ancillary co-ligand.
 11. The method according to claim 10, wherein the catalyst is at least one selected from the group consisting of Ru(TMBTP)(OCOCF₃)₂; Ru(TMBTP)(p.cymene)I₂; Ru(TMBTP)(p.cymene)Cl₂; Ru(BINAP)(OCOCF₃)₂; Rh(COD) (Chiraphos)ClO₄; and Rh(NBD)(Chiraphos)ClO₄; where TMBTP denotes 2,2′,5,5′tetramethyl,3,3′bis(diphenylphosphine), 4.4′bithiophene, BINAP denotes 2,2′bis(diphenylphosphine)1,1′binaphthyl, Chiraphos denotes 2,3 bis(diphenylphosphine)butane, COD denotes cyclooctadiene, and NBD denotes norbornadiene.
 12. The method according to claim 1, wherein the enantioselective hydrogenation is carried out at a pressure of 1-100 bar.
 13. The method according to claim 12, wherein the pressure is 1-20 bar.
 14. The method according to claim 1, wherein the enantioselective hydrogenation is carried out at a temperature of 20-100° C.
 15. The method according to claim 14, wherein the temperature is 20-60° C.
 16. The method according to claim 1, wherein enantioselective hydrogenation is carried out in the presence of a solvent or a solvent mixture.
 17. The method according to claim 16, wherein the solvent is at least one selected from the group consisting of C₁-C₄ alcohols, tetrahydrofuran, methylene chloride, C₁-C₄ alkyl aromatics, C₆-C₁₀ alkanes and their mixtures with water.
 18. The method according to claim 1, wherein in the compound of formula (I) W is a C═O group; X is OH or O⁻M⁺ in which M⁺ has the meanings already indicated above; Z is OH, N(iC₃H₇)₂ or O⁻M⁺ in which M⁺ has the meanings already indicated above.
 19. The method according to claim 1, wherein in the compound of formula (II) W is a CH₂ or C═O group; Y is OH or O⁻M⁺ in which M⁺ has the meanings already indicated above; T is OH, N(iC₃H₇)₂ or O⁻M⁺ in which M⁺ has the meanings already indicated above.
 20. The method according to claim 19, wherein Y and T, together, represent an oxygen atom of the lactone of formula (IIA) 